Sickle cell disease is the most common hemoglobinopathy in the world, and, in the* United States, affects approximately 1 in 360 African Americans and 1 in 1200 Latinos. Small vessel occlusion, or vaso-occlusion, is the primary pathology leading to clinical complications of this disease. The most frequent manifestation of vaso-occlusion is the acute pain episode (crisis), which often requires hospitalization and narcotic use, thus exacting an economic, social, and psychological toll on afflicted individuals. Standard of care is inadequate, there being no specific therapies that target ongoing acute pain episodes. Mouse models have shown that leukocytes adherent to blood vessel endothelium play a crucial role in vaso-occlusion, probably through their subsequent interaction with sickle red blood cells. Further work, to which I contributed, has shown that intravenous gammaglobulin (IVIG) administered either prior to or after the induction of vaso-occlusion rapidly and dramatically reduces leukocyte adhesion to endothelium and subsequent red cell interactions, leading to a marked increase in survival. Based on this work , I plan to develop my skills as a clinical investigator by conducting a randomized, double-blind, placebo-controlled, dose-escalation Phase l-ll trial to study the safety and efficacy of a single dose of IVIG compared to normal saline placebo administered to patients with sickle cell anemia admitted to the hospital with an uncomplicated acute pain episode. A total of 52 subjects will be enrolled. I hypothesize that IVIG will act quickly to reduce vaso-occlusion and thus pain scores, narcotic use, and length of hospitalization. I will also investigate the physiological effects of IVIG in patients with sickle cell disease by measuring the adhesion receptors involved in leukocyte adherence to endothelium and red blood cell- leukocyte interactions, microcirculatory blood flow, and serum markers of hemolysis. Completion of this trial, along with further formal training in biostatistics and translational science coursework, research seminars, and the mentorship of experienced clinical investigators, will prepare me to become an independent clinical investigator focusing on translational bench-to-bedside work. It will also allow me to submit by the end of the training period an NIH application to expand this trial into a Phase III trial or to test, in Phase l-ll trials, newly identified agents that interfere with the molecular mechanism of vaso-occlusion. (End of Abstract)